1. Significant excretion of glucocerebroside via the bile in patients with Gaucher's disease has been demonstrated. This observation is consistent with our previous finding that only a small portion of the daily turnover or glucocerebroside accumulates and contributes to the pathogenesis of Gaucher's disease. We propose to investigate how this excretory pathway might be augmented in order to reduce the accumulation of lipid in this hereditary metabolic disorder. 2. The chemical synthesis of the cyanohydrin derivative of glucocerebroside has been accomplished. We intend to use this compound to select for mutant cells deficient in glucocerebrosidase to develop an animal model of Gaucher's disease. 3. We have demonstrated the catabolism of accumulated sphingomyelin by exogenous sphingomyelinase in tissue specimens from our animal model of human Type C Niemann-Pick disease and we have improved our procedure for the isolation of sphingomyelinase from human placental tissue in order to pursue enzyme replacement in Niemann-Pick disease.